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ILC2 Transfers to Apolipoprotein E Deficient Mice Reduce the Lipid Content of Atherosclerotic Lesions

Overview

Overview

Journal BMC Immunol

Publisher Biomed Central

Specialty Allergy & Immunology

Date 2019 Dec 12

PMID 31823769

Citations 12

Authors

Authors

Polyxeni T Mantani

Pontus Duner

Irena Ljungcrantz

Jan Nilsson

Harry Bjorkbacka

Gunilla Nordin Fredrikson

Affiliations

Affiliations

Soon will be listed here.

Abstract

Background: Expansion of type 2 innate lymphoid cells (ILC2s) in hypercholesterolaemic mice protects against atherosclerosis while different ILC2 subsets have been described (natural, inflammatory) based on their suppression of tumorigenicity 2 (ST2) and killer-cell lectin like receptor G1 (KLRG1) expression. The aim of the current study is to characterize the interleukin 25 (IL25)-induced splenic ILC2 population (LinCD45IL17RBICOSIL7ra) and address its direct role in experimental atherosclerosis by its adoptive transfer to hypercholesterolaemic apolipoprotein E deficient (apoE) mice.

Results: Immunomagnetically enriched, FACS-sorted ILC2s from the spleens of IL-25 treated apoE mice were stained for KLRG1 and ST2 directly upon cell obtainment or in vitro cell expansion for flow cytometric analysis. IL25-induced splenic ILC2s express high levels of both KLRG1 and ST2. However, both markers are downregulated upon in vitro cell expansion. In vitro expanded splenic ILC2s were intraperitoneally transferred to apoE recipients on high fat diet. ApoE mice that received in vitro expanded splenic ILC2s had decreased lipid content in subvalvular heart and brachiocephalic artery (BCA) plaques accompanied by increased peritoneal B1 cells, activated eosinophils and alternatively activated macrophages (AAMs) as well as anti-phosphorylcholine (PC) immunoglobulin (Ig) M in plasma.

Conclusions: With the current data we designate the IL25-induced ILC2 population to decrease the lipid content of atherosclerotic lesions in apoE mice and we directly link the induction of B1 cells and the atheroprotective anti-PC IgM antibodies with ILC2s.

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References

1.

Huang Y, Guo L, Qiu J, Chen X, Hu-Li J, Siebenlist U . IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells. Nat Immunol. 2014; 16(2):161-9. PMC: 4297567. DOI: 10.1038/ni.3078. View

2.

Neill D, Wong S, Bellosi A, Flynn R, Daly M, Langford T . Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature. 2010; 464(7293):1367-70. PMC: 2862165. DOI: 10.1038/nature08900. View

3.

Taleb S, Tedgui A, Mallat Z . IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles. Arterioscler Thromb Vasc Biol. 2014; 35(2):258-64. DOI: 10.1161/ATVBAHA.114.303567. View

4.

Molofsky A, Nussbaum J, Liang H, Van Dyken S, Cheng L, Mohapatra A . Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med. 2013; 210(3):535-49. PMC: 3600903. DOI: 10.1084/jem.20121964. View

5.

Whitman S, Ravisankar P, ELAM H, Daugherty A . Exogenous interferon-gamma enhances atherosclerosis in apolipoprotein E-/- mice. Am J Pathol. 2000; 157(6):1819-24. PMC: 1885762. DOI: 10.1016/s0002-9440(10)64820-1. View

6.

Tsimikas S, Brilakis E, Lennon R, Miller E, Witztum J, McConnell J . Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events. J Lipid Res. 2006; 48(2):425-33. DOI: 10.1194/jlr.M600361-JLR200. View

7.

Caligiuri G, Nicoletti A, Poirier B, Hansson G . Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J Clin Invest. 2002; 109(6):745-53. PMC: 150903. DOI: 10.1172/JCI7272. View

8.

Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H . Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature. 2009; 463(7280):540-4. DOI: 10.1038/nature08636. View

9.

Tsimikas S, Willeit P, Willeit J, Santer P, Mayr M, Xu Q . Oxidation-specific biomarkers, prospective 15-year cardiovascular and stroke outcomes, and net reclassification of cardiovascular events. J Am Coll Cardiol. 2012; 60(21):2218-29. DOI: 10.1016/j.jacc.2012.08.979. View

10.

Wardemann H, Boehm T, Dear N, Carsetti R . B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen. J Exp Med. 2002; 195(6):771-80. PMC: 2193734. DOI: 10.1084/jem.20011140. View

11.

Kyaw T, Tay C, Krishnamurthi S, Kanellakis P, Agrotis A, Tipping P . B1a B lymphocytes are atheroprotective by secreting natural IgM that increases IgM deposits and reduces necrotic cores in atherosclerotic lesions. Circ Res. 2011; 109(8):830-40. DOI: 10.1161/CIRCRESAHA.111.248542. View

12.

Davies M, Richardson P, Woolf N, Katz D, Mann J . Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J. 1993; 69(5):377-81. PMC: 1025095. DOI: 10.1136/hrt.69.5.377. View

13.

Mantani P, Duner P, Bengtsson E, Alm R, Ljungcrantz I, Soderberg I . IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice. PLoS One. 2015; 10(1):e0117255. PMC: 4309452. DOI: 10.1371/journal.pone.0117255. View

14.

Goncalves I, den Ruijter H, Nahrendorf M, Pasterkamp G . Detecting the vulnerable plaque in patients. J Intern Med. 2015; 278(5):520-30. DOI: 10.1111/joim.12414. View

15.

Newland S, Mohanta S, Clement M, Taleb S, Walker J, Nus M . Type-2 innate lymphoid cells control the development of atherosclerosis in mice. Nat Commun. 2017; 8:15781. PMC: 5467269. DOI: 10.1038/ncomms15781. View

16.

Oliphant C, Hwang Y, Walker J, Salimi M, Wong S, Brewer J . MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity. 2014; 41(2):283-95. PMC: 4148706. DOI: 10.1016/j.immuni.2014.06.016. View

17.

Buono C, Come C, Stavrakis G, Maguire G, Connelly P, Lichtman A . Influence of interferon-gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse. Arterioscler Thromb Vasc Biol. 2003; 23(3):454-60. DOI: 10.1161/01.ATV.0000059419.11002.6E. View

18.

Gupta S, Pablo A, Jiang X, Wang N, Tall A, Schindler C . IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest. 1997; 99(11):2752-61. PMC: 508122. DOI: 10.1172/JCI119465. View

19.

Cardilo-Reis L, Gruber S, Schreier S, Drechsler M, Papac-Milicevic N, Weber C . Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype. EMBO Mol Med. 2012; 4(10):1072-86. PMC: 3491837. DOI: 10.1002/emmm.201201374. View

20.

Bobryshev Y, Ivanova E, Chistiakov D, Nikiforov N, Orekhov A . Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis. Biomed Res Int. 2016; 2016:9582430. PMC: 4967433. DOI: 10.1155/2016/9582430. View